3-119876656-A-T

Variant names:

• chr3-119876656-A-T
• rs1719895
• NM_001146156.2:c.814-148T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002093.4(GSK3B):​c.814-148T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSK3B NM_002093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 9 publications found

Genes affected

GSK3B (HGNC:4617): (glycogen synthase kinase 3 beta) The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

GSK3B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	NM_001146156.2	MANE Select	c.814-148T>A		intron	N/A	NP_001139628.1
	GSK3B	NM_002093.4		c.814-148T>A		intron	N/A	NP_002084.2
	GSK3B	NM_001354596.2		c.814-148T>A		intron	N/A	NP_001341525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSK3B	ENST00000264235.13	TSL:1 MANE Select	c.814-148T>A		intron	N/A	ENSP00000264235.9
	GSK3B	ENST00000316626.6	TSL:1	c.814-148T>A		intron	N/A	ENSP00000324806.5
	GSK3B	ENST00000678439.1		c.814-148T>A		intron	N/A	ENSP00000503868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000222 AC: 1 AN: 450774 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 239464

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12342

American (AMR) AF: 0.00 AC: 0 AN: 19126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13646

East Asian (EAS) AF: 0.00 AC: 0 AN: 31024

South Asian (SAS) AF: 0.00 AC: 0 AN: 43670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1948

European-Non Finnish (NFE) AF: 0.00000369 AC: 1 AN: 271022

Other (OTH) AF: 0.00 AC: 0 AN: 26032

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 34727

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.55
DANN	Benign	0.12
PhyloP100		-2.7
PromoterAI		-0.012	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1719895; hg19: chr3-119595503;